Abstract (Microscopy Core) The Microscopy Core of the Indiana Diabetes Research Center (IDRC) will support the needs of center investigators for high-resolution and quantitative optical microscopy, providing training and access to advanced forms of light microscopy and digital image analysis. The comprehensive facilities and the expertise of the Microscopy Core will provide IDRC investigators with the capability to conduct quantitative microscopy studies at the highest level. Core personnel will work closely with IDRC investigators to develop imaging strategies that may include wide-field microscopy, confocal microscopy, multi-photon microscopy, and digital deconvolution microscopy, depending on the needs of the research study. Fastidious attention to equipment maintenance, user training and data evaluation by this centralized core will provide for consistent quality and reliable interpretation of data. A major focus of the Microscopy Core will be to implement cutting- edge techniques in optical microscopy, allowing them to be used effectively by IDRC researchers who might have limited experience with microscopy. Specifically, the Core will apply and adapt methods of intravital microscopy that the ICBM has developed over the past 12 years to studies of the pathophysiology of diabetes and will develop and implement novel assays of protein and cell function based upon fluorescent protein biosensors, applying a combined approach of spectral and time-resolved fluorescence quantification. The aims of the core include: (1) Conduct microscopy studies for laboratories lacking microscopy expertise; adapt, optimize and validate existing protocols. (2) Develop protocols and provide training in challenging forms of microscopy, including live-cell imaging, quantitative digital image analysis and 3D/4D microscopy for laboratories experienced with microscopy (3) Work with IDRC investigators to develop and validate protocols and reagents for quantitative microscopy of fluorescent protein biosensors. (4) Work with IDRC investigators to develop and validate procedures for intravital microscopy of the pancreas, and of islets transplanted to the kidney capsule or anterior chamber of the eye. (5) Provide ongoing consultation and guidance on the design and analysis of new microscopy studies. The Microscopy Core will constitute an invaluable resource for the IDRC, providing investigators with the equipment and support necessary to conduct microscopy at the highest level, combined with a program of methods development that will provide them with effective access to unique and powerful research capabilities that are currently limited to the relatively few laboratories that specialize in microscopy.